摘要
目的观察2型糖尿病大鼠视网膜正性转录延伸因子b(P-TEFb)蛋白的表达及小檗碱对其的影响。方法链脲佐菌素(35mg·kg^(-1),ip)诱导糖尿病大鼠模型,2 wk后予高糖高脂饲料喂养共14 wk。wk 17起,大鼠共分为7组,每组10只:A组(不予链脲佐菌素且用标准饲料喂养,不予药物治疗),B组(不予药物治疗),C、D、E组(分别予小檗碱75、150、300 mg·kg^(-1)·d^(-1)),F组(予非诺贝特100 mg·kg^(-1)·d^(-1))和G组(予罗格列酮4mg·kg^(-1)·d^(-1)),连续给药16 wk。处死大鼠,采用HE染色检查视网膜结构变化,免疫组化检测P-TEFb的表达,P-TEFb由细胞周期蛋白依赖激酶9(CDK9)和细胞周期蛋白T1 (cyclin T1)组成。结果正常对照组大鼠的视网膜厚度大于其他各组,经中、高剂量小檗碱(150、300 mg·kg^(-1))和罗格列酮治疗能增加糖尿病视网膜的厚度,但视网膜的结构在各组间无差别。中、高剂量小檗碱和罗格列酮都能明显促进糖尿病大鼠视网膜中CDK9和cyclin T1蛋白表达(P<0.01),但低剂量小檗碱(75mg·kg^(-1))和非诺贝特对糖尿病视网膜中CDK9和cyclin T1的表达没有影响(P>0.05)。结论小檗碱调控视网膜P-TEFb(CDK9和cyclin T1)蛋白的表达可能是其改善糖尿病视网膜病的机制之一。
AIM To investigate the positive the effect of berberine on diabetic retina of the rat. transcription elongation factor b （P-TEFb） expression and METHODS Type 2 diabetes mellitus rat models were induced by injection （ip） with streptozotocin （STZ） 35 mg·kg^-1 and 2 wk later followed by a high-carbohydrate/ high-fat diet for 14 wk. From wk 17, the rats were divided into 7 groups with 10 rats in each： age-matched non diabetic control rats （group A） that neither received STZ nor the high-carbohydrate/high-fat diet; 16-wk diabetic rats without any drug treatment （group B） ; diabetic rats treated with berberine at a dose of 75, 150 or 300 mg·kg^-1 every day （group C, group D, and group E, respectively）; diabetic rats treated with fenofibrate at a dose of 100 mg·kg^-1 or rosiglitazone at a dose of 4 mg·kg^-1 every day （group F and group G both served as positive control）. After 16 wk treatment, the retinal structure was observed with hematoxylin-eosin （HE） staining and P-TEFb （cyclin-dependent kinases 9 （CDK9） and cyclin T1） protein expression was detected by immunohistochemistry. RESULTS The retinas of control group were thicker than those of other 6 groups. After 16 wk treatment of middle-, high-dose berberine and rosiglitazone, the diabetic retinas showed increase of thickness but no difference in retinal structure among all groups. Middle-, high-dose berberine and rosiglitazone promoted significantly CDK9 and cyclin T1 expression in diabetic retinas （P 〈 0.01 ）, but low-dose berberine and fenofibrate showed no effect on CDK9 and cyclin T1 expression. CONCLUSION Berberine modulating P-TEFb level in diabetic retina may probably be one of the mechanisms to ameliorate retinopathy induced by STZ and the high-carbohydrate/high-fat diet.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2008年第4期243-248,共6页
Chinese Journal of New Drugs and Clinical Remedies
